recent advances in the discovery of haem-targeting drugs for malaria and schistosomiasis最近的发现进步haem-targeting针对疟疾和血吸虫病的药物.pdfVIP

Molecules 2009, 14, 2868-2887; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Recent Advances in the Discovery of Haem-Targeting Drugs for Malaria and Schistosomiasis 1, 2 Katherine A. de Villiers * and Timothy J. Egan 1 University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa 2 University of Cape Town, Private Bag, Rondebosch 7701, South Africa; E-mail: timothy.egan@uct.ac.za (T.J.E.) * Author to whom correspondence should be addressed; E-mail: kchen@sun.ac.za Received: 30 June 2009; in revised form: 20 July 2009 / Accepted: 22 July 2009 / Published: 4 August 2009 Abstract: Haem is believed to be the target of some of the historically most important antimalarial drugs, most notably chloroquine. This target is almost ideal as haem is host- derived and the process targeted, haemozoin formation, is a physico-chemical process with no equivalent in the host. The result is that the target remains viable despite resistance to current drugs, which arises from mutations in parasite membrane transport proteins. Recent advances in high-throughput screening methods, together with a better understanding of the interaction of existing drugs with this target, have created new prospects for discovering novel haem-targeting chemotypes and for target-based structural design of new drugs. Finally, the discovery t